Substituted alkylsulfonylimidazoles



United States Patent 3,499,001 SUBSTITUTED ALKYLSULFONYLIMIDAZOLESAlbert William Lutz, Montgomery Township, Somerset County, N.J.,assignors to American Cyanamid Company, Stamford, Conn., a corporationof Maine No Drawing. Filed July 21, 1967, Ser. No. 654,968 Int. Cl. C07d49/36; A01n 9/22 US. Cl. 260309 10 Claims ABSTRACT OF THE DISCLOSURESubstituted alkylsulfonylimidazole compounds of the formula:

This invention relates to new alkylsulfonylimidazole compounds, to amethod for preparing intermediates required in the preparation ofcertain of said new compounds, and to methods of controlling undesirableplant growth by use of the new compounds.

The new compounds of the invention may be depicted by the formula:

wherein R is a member selected from the group consisting of alkyl,alkenyl and aralkyl and X and Y are hydrogen, nitro or halogen, at leastone of X and Y being halogen. Preferred alkyl groups are lower alkyl (C-C particularly those containing from 1 to 4 carbon atoms. Halogen inthe definition of X and Y includes chlorine, bromine and iodine. Fromthe foregoing definition it should be understood that X and Y may be thesame or different halogens and X or Y may be hydrogen or nitro providedthat the other of X and Yis halogen.

The compounds of the invention include the obvious equivalents ofFormula I compounds, particularly the tautometric forms and salts bothof Formula I compounds and of the tautomers. Preferred salts are thewatersoluble salts such as the alkali metal (e.g., sodium, potassium)and ammonium salts.

The following are typical of the compounds of the invention. Thenumbering of the substituents on the imidazole ring corresponds with thenumbering shown in Formula I above.

2-methylsulfonyl-4,S-dichloroimidazole2-metbylsulfonyl-4,S-dibromoimidazole2-n-butylsulfonyl-4,S-diiodoimidazole2-methylsulfonyl-4-chloro-5-bromoimidazole2-ethylsulfonyl-4-chloro-5-nitroimidazole2-n-propylsu1fonyl-4-chloro-S-iodoimidazole iceZ-n-butylsulfonyl-4-nitro-5-bromoimidazole2-methylsulfonyl-4-nitro-5-iodoimidazole2-methylsulfonyl-4-bromo-5-iodoimidazole2-isopropylsulfonyl-4,S-dichloroimidazole 2-methylsulfonyl-4bromoimidazole Z-methylsulforiylA-chloroimidazole2-n-butylsulfonyl-4-iodoimidazole 2-isobutyl-4,S-dichloroimidazole Thepreferred herbicidal compounds are the 2-loweralkylsulfonyl-4,5-substituted imidazoles in which the and 5 substituentsare either chlorine or bromine, for example:

2-methylsu1fonyl-4,5dichloroimidazole2-methylsulfonyl-4,S-dibromoimidazole2-methylsulfonyl-4-chloro-S-bromoimidazole Compounds of Formula I areprepared by the reaction of Z-mercaptoimidazole with an alkyl halide inan alkaline aqueous-alcoholic solution to produce 2-alkylthioimidazoleas shown in A below wherein R is as defined above and X is halogen.

U1 SH m If it is desired that X or Y be nitro, the2-alkylthioimidazole 1) is dissolved in concentrated nitric acid.Concentrated sulfuric acid is then added to the resulting solution andthe reactants are heated for suflicient time to produce2-alkylthio-4-nitroimidazole as shown in B below. N NO N Q L as. TL L SR+HNO3 SR N N H H (2) The next synthesis step is the oxidation of eitherthe 2-alkylthioimidazole 1 or 2-alkylthio-4-nitro-imidazole 2 to theappropriate 2-alkylsulfonylimidazole. This is accomplished byreactingeither 1 or 2 with typical oxidizing agents such asm-chloroperbenzoic acid, monoperphthalic acid, peracetic acid, hydrogenperoxide, or aqueous or alcoholic chlorine solutions, in an inertorganic solvent as illustrated in Reactions C and D below.

Although most common oxidizing agents will sufiice to produce thedesired Products 3 and 4, the form in which the product is produced hasbeen found to vary markedly depending upon which oxidizing agent isemployed. For example, the product ordinarily produced by the majorityof oxidizing agents is an oily liquid mass which, in addition to thedesired product, contains several other species of chemical compositionas indicated by infra-red analytical techniques. The purification andisolation of the desired Product 3 or 4 from this oily mass is extremelydifficult and impractical. However, when m-chloroperbenzoic acid ormono-perphthalic acid is employed as the oxidizing agent, the desiredproduct is surprisingly formed as a distinctly solid precipitate whichupon analysis is found to contain the desired product plus spentoxidizing agent. The solid material is readily purified usingconventional methods.

Other conditions of Reactions C and D are noncritical. For example,while the reaction readily occurs with stoichiometric amounts of theimidazole and OXidiZing agent, it is preferred to employ an excess ofoxidizing agent. Preferred inert organic solvents are the lower alkanolssuch as methyl, ethyl and isopropyl alcohols, singly or in admixturewith other inert solvents. The reaction may be effected above or belowroom temperature or at subor super-atmospheric pressures although itoccurs readily at room temperature and atmospheric pressure. Order ofaddition is not critical but it is preferred to add the oxidizing agentto the imidazole solution. Reaction is substantially complete afteraddition of the oxidizing agent and no substantial advantage is gainedby prolonging the reaction.

The final synthesis step for preparing compounds of Formula I involvessubstitution of the desired X and/or Y halogen in the 4 and/ or 5position of the imidazole ring of Compounds 3 and 4 as illustrated inthe examples below. These examples are not intended to limit theinvention except as defined in the appended claims. All parts andpercentages are by weight unless otherwise indicated.

EXAMPLE 1 Preparation of Z-methylthioimidazole Z-mercaptoimidazole (10.0grams) was dissolved in 100 milliliters of a 1.0 N aqueous sodiumhydroxide solution. A solution of methanolic methyl iodide (10.0 gramsof methyl iodide dissolved in 100 milliliters of methanol) was addedrapidly to the above solution with stirring. The reactants were held oneto two hours at room temperature with stirring. The precipitate was thenremoved by filtration and air dried. After recrystallization from ethylacetate, 8.1 grams of Z-methylthioimidazole (71% yield) were obtainedwith a melting point of 136.5-138" C.

The above procedure is followed in all essential respects except forsubstitution of the appropriate alkyl halide or alkylthioalkyl halidefor methyl iodide to yield:

2-(butylthio)imidazole, M.P. 71-72 C. '2-(allylthio)imidazole, M.P.70-71 C. 2-[2-(methylthio)ethylthio1imidazole, M.P. 90-92 C. or2-(dodecylthio)imidazole, M.P. 58-60 C.

EXAMPLE 2 Preparation of 2-methylthio-4-nitroimidazo1e 8.0 grams ofZ-methylthioimidazole are dissolved in 16 milliliters of concentratednitric acid followed by the addition, with cooling, of 16 milliliters ofconcentrated sulfuric acid. As soon as the initial reaction subsides,the reactants are heated for two hours. The solution is then cooled andpoured into ice water. The solid product, 2-methylthio-4-nitroimidazole, is c llected by filtration and recrystallized 4 EXAMPLE3 Preparation of Z-methylsulfonylimidazole l N L J-SOsCHs To a solutionof Z-methylthioimidazole (5.0 grams in milliliters of ethanol) was addedwith stirring and in a dropwise manner a solution of m-chloroperbenzoicacid (17.8 grams in 100 milliliters of ethanol). After the solutionaddition was complete, sufiicient sodium sulfite was added to destroyany excess peroxide (as determined by the standard starch-iodide test).The solvent was removed under vacuum and the white solid residue wasextracted with ether to remove m-chlorobenzoic acid. The undissolvedsolid was recrystallized from methanol to give 4.9 grams (76.5% yield)of product with a melting point of 213-215 C.

Analysis-Calculated for C H N 0 S: C, 32.88; H, 4.14; N, 19.18; S,21.94%. Found: C, 32.56; H, 3.98; N, 19.14; S, 22.01%.

The above procedure is followed in all essential respects except forsubstitution of the appropriate 2-alkylthioimidazole,2-arylthioimidazole or 2-[2-(alkylthio) alkylthio] imidazole for2-methylthioimidazole to yield:

EXAMPLE 4 Preparation of 2-methylsulf0nyl-4,5-dibromoimidazole BrN2-methylsulfonylimidazole (0.73 grams) was dissolved in 20 millilitersof 1. 0 N sodium hydroxide solution and with stirring, bromine (1.60grams) in 5 milliliters of chloroform was added dropwise whilemaintaining the temperature at about 25 C. After the addition wascomplete, a small amount of sodium bisulfite was added to discharge thecolor. The colorless aqueous layer was acidified to a pH of 1-2 withconcentrated sulfuric acid and chilled to cause the precipitation of 1.0gram (66% yield) of product a spale yellow needles with a melting pointof 202-204 C. The product was dissolved in water and charcoal treated,and was then recrystallized from water to yield a white solid with amelting point of 211-212 C.

Analysis-Calculated for C H Br N O S: C, 15.80; H, 1.33; N, 9.22; Br,52.58%. Found: C, 16.05; H, 1.31; N, 9.29; Br, 52.31%.

The above procedure is followed in all essential respects except forsubstitution of the appropriate 2-alkylsulfonylimidazole,2-arylsulfonylimidazole or 2-[(2-alkyl sulfonyl)alkylsulfonynimidazolefor 2 methylsulfonylimidazole to yield:

2-(benzylsulfonyl)-4,5-dibromoimidazole, M.P. 234- 4,5 -dibromo-2 2-methylsulfonyl) ethylsulf onyl] imidazole, M.P. 233-235 C.

4,5-dibromo-2-(ethylsulfonyDimidazole, M.P. 209-4,5-dibromo-2-(bntylsulfonylfimidazole, "M.P. 159- 4,5-dibromo-2-2,4-dinitrophenyl) sulfonyl] imidazole2-(allylsulfonyl)-4,5-dibromoimidazole, M.P. -190 C.

2- (dodecylsulfonyl) -4,S -dibromoimidazo1e.

EXAMPLE Preparation of 2-methylsulfonyl-4,5-dichloroimidazole and2-methylsulf0nyl-4-bromo-5-ch1oroimidazole Cl Tl Br ll CllN SOZCH: CllNSO2CH;

2-methylsulfonyl-4,S-dibromoimidazole (20.0 grams) was refluxed in 500milliliters of concentrated hydrochloric acid for 24 hours withstirring. The reaction solution was diluted with 500 milliliters ofwater and then concentrated to a 300 milliliter volume. The pH wasadjusted to 2.5-3.0 with ammonium hydroxide followed by chilling. Thedried precipitate (8.1 grams) had a melting point of 178-181" C.Analysis by mass spectroscopy showed the product to contain 92%2-methylsulfonyl-4,S-dichloroimidazole and 7%2-methylsulfonyl-4-bromo-5-chloroimidazole.

A reduction in the reflux period increased the yield of the4-bromo-5-chloro compound. For example, a 6-hour reflux period gave aproduct containing as much as 4 0%2-methylsulfonyl-4-bromo-5-ch1oroimidazole.

EXAMPLE 6 Preparation of 2-methylsulfonyl-4-chloroimidazole 10.0 gramsof 2-methylsulfonyl-4-bromo5-chloroimidazole are refluxed in 100milliliters of 20% aqueous sodium sulfite solution. The reactants arethen chilled, the pH adjusted to 2, and the desired product isolated andpurified in the usual manner.

EXAMPLE 7 Preparation of 2-methylsulfonyl-4-iodoimidazole The procedureof Example 4 is repeated except that bromine is replaced by oneequivalent of iodine to give 2-methylsulfonyl-4-iodoimidazole.

EXAMPLE 8 Preparation of 2-methylsulfonyl-4-iodo-S-bromoimidazole I -N Br-L J-SOzCHa EXAMPLE 9 Preparation of2-methylsulfonyl-4-nitro-5-bromoimidazole NO2---N Brl lSOzCH:

The procedure of Example 4 is repeated except that 2-methylsulfonylimidazole is replaced by Z-methylsulfonyl-4-nitroimidazole and a stoichiometric quantity of bromine is added toyield 2-methylsulfonyl-4-nitro-5-bromoimidazole.

The compounds of the invention are highly active preemergence andpost-emergence herbicides. They may be dissolved or dispersed in knownliquid carriers and applied in liquid sprays to the foliage of the plantor to the soil containing seeds of the plants to be controlled. They mayalso be applied as solids in dust or granular formulations withconventional application equipment. The proportions of compounds in suchformulations, whether liquid or solid, are conventional and in generalwill be amounts effective to provide the herbicidal activity. Ifdesired, other additives, such as pesticides and wetting agents, may beemployed with the herbicidal compounds.

It has surprisingly been observed that the alkyl sulfonyl group in thecompounds appears responsible for the excellent herbicidal activity,both against broad and narrow leaf plant species. The reason for this isthat when the alkyl sulfonyl group is replaced with certain other groupssuch as methyl and ethyl, the herbicidal activity of the compounds iseither insignificant or substantially inferior to that of the alkylsulfonyl substituted imidazoles, all other things being equal. Examples10 and 11 illustrate the utility of compounds of the invention.

EXAMPLE 10 The pre-emergence herbicidal activity of the com pounds ofthe invention is exemplified by the following tests in which the seedsof a variety of monocotyledonous and dicotoyledonous plants areseparately mixed with potting soil in separate pint cups. Afterplanting, the cups are sprayed with the selected aqueous-acetonesolution containing small amounts of a wetting agent and the testcompound in suificient quantity to provide the equivalent of 2 or 1 0pounds per acre of test compound per cup. The treated cups are thenplaced on greenhouse benches and cared for in the usual manner, inaccordance with greenhouse procedures. Two weeks after treatment, thetests are terminated and each cup is examined and rated, as shown inTable I, according to the Herbitoxicity Index defined below.

Herbitoxicity index 9=100% reduction in stand 9-=1 or 2 stunted plantsremaining 8=85-100% reduction in stand 7=7085% reduction in stand6=6070% reduction in stand 5=50-60% reduction in stand 4=40-50%reduction in stand 3=30-40% reduction in stand 2=20-30% reduction instand 1=l020% reduction in stand O=no apparent effect s=severe injuryIn: moderate injury t=trace of slight injury =no test r=regrowthAbbreviations for plant species employed in the herbicidal activitytests of Examples 10 and 11 are as follows: BiBindweed CTCanada ThistleJGJohnson Grass NS-Nutsedge QG-Quackgrass Ko-Kochia LaLambsquartersMu-Mustard Pi-Pigweed Ba--Barnyardgrass CrCrabgrass GF-Green FoxtailWOWild Oats Mi-Millet Ra-Radish TABLE I.PRO-EMERGENCE Plant species RateTestcompound (lbs/acre) K La Mu Pi Ba Cr GF W0 Mi Ra Br 2 8 5m 8 9 t 59" 9 10 9- 9' 9 9 8S 9 9 9 l i N B! H SOzCHa G1 10 8s 8s 9 9 m s 55 9- Ii N Cl H SO2CH N Br SOaGHal T N I?! SO2CHZCH=CH2 Br 25 9c o 9- H Br30204 9 fir 25 9- 9 9- l T iii k Br 803 2 6 EXAMPLE 11 duceconcentrations of about 0.4, 2, or 10 pounds per acre of active compoundwhen applied to the plants through a a spray nozzle operating at 30p.s.i. for a predetermined time. After spraying, the plants are placedon greenhouse benches and are cared for in the usual manner,commensurate with conventional greenhouse practices. Two weeks aftertreatment, the seedling plants are examined and rated in Table 11 belowaccording to the Herbitoxicity Index defined above.

TAB LE II.-POST EME RGEN GE gist? Plant species s. Test compound acre)BW CT J G NS Q G K0 La Mu Pi Ba Cr GF W0 Br 0. 4 0 t 9 t o o t t 2 S, r9 O 0 0 9 9 9 9 t t 9- 9 T? 10 9 t 0 9 9 9 9 9 9 9 9 9 N Br H SOzC a Cl0 9 0 0 0 0 t t s 9 m 0 O m 9- T1 9 9 9 m 0 8 9 L 01 H 502GB;

B1- 10 9 9 0 t t TABLE IICntinued (lllbatrlz Plant species Test compoundacr e) BW CT JG NS QG K0 La Mu Pi Ba Cr GF WO Br 9 9 9 9 S 9SO2-CH2CH=CH N 2 Br Br 10 S S t S m t /LN -SOgC 1Hn-n Br ll /\N/ S02C1H5Br I claim: 8. The compound according to claim 1 which is 1. A compoundof the formula: 2-methylsulfonyl-4,5-dich1oroimidazole.

X 9. The compound according to claim 1 which isZ-ethylsulfonyl-4,S-dibromoimidazole. Y 502R 10. The compound accordingto claim 1 which is 1\|I/ 2-allylsulfonyl-4,S-dibromoimidazole. Hwherein R is a member selected from the group consist- References Citeding of alkyl of from 1 to 12 carbon atoms, lower alkenyl, UNITED STATESPATENTS and benzyl; X and Y are hydrogen, nitro or ha ogen, 3,341,5499/1967 Henry 260-309 with at least one of X and Y being halogen.

2. The compound of claim 1 wherein X and Y are OTHER REFERENCESchlorine. Merck Chem. Abstn, vol. 63, cols. 608-9 (1965).

3. The compound of claim 1 wherein X and Y are Wagner et al., SyntheticOrganic Chemistry, p. 801, bromine. New York, Wiley, 1953,

4. The compound of claim 1 wherein X is chlorine d Y i b i HENRY B.JILES, Primary Examlner 5. The compound of claim 1 wherein X is chlorineNATALIE TROUSOF, Assistant Examiner and Y is hydrogen.

6. The compound of claim 1 wherein X is bromine US. Cl. X.R. and Y ishydrogen. 7l-92 7. The compound according to claim 1 which is2-methsulfony14,S-dibromoimidazole.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No-3,499,oo1 Dated March 19, 1970 Inventor) ALBERT WILLIAM LU'IZ It iscertified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

Column 2, line 10 following the term "the" insert the numeral --R--.

Column 2, line 53 cancel that part of the formula which reads "ClC H COOG" and insert --ClC,H CO OH--.

Columns 7 and 8, Table I please change the title to read Pre-emergence.

Signed and sealed this 28th day of July 1970.

(SEAL) Attestz EDWARD M.PLETCHER JR. 7 WILLIAM E. SCHUYLER JR AttestingOfficer Commissioner of Patents

